1. Field of the Invention
The present invention relates to a planar waveguide grating (PWG) sensor which exhibits a low signal drift and an enhanced sensitivity due to the use of a fully dense silicon rich silicon nitride surface layer. In addition, the present invention relates to a method for manufacturing the PWG sensor with acceptable costs and high yields by utilizing well known semiconductor processes and tools.
2. Description of Related Art
The following abbreviations are herewith defined, at least some of which are referred to in the ensuing description of the prior art and the preferred embodiments of the present invention.
APCVDAtmospheric Pressure Chemical Vapor DepositionCVDChemical Vapor DepositionFIBFocused Ion BeamFSGFluorine Doped Silica GlassLPCVDLow Pressure Chemical Vapor DepositionPECVDPlasma Enhanced Chemical Vapor DepositionPWGPlanar Waveguide GratingPVDPhysical Vapor DepositionRIEReactive Ion EtchingSACVDSub-Atmospheric Chemical Vapor DepositionSEMScanning Electron MicroscopySPRSurface Plasmon ResonanceUVUltraviolet
Evanescent field-based sensors are fast becoming a technology of choice for accurate label-free detection of a biological, biochemical, or chemical substance (e.g., cells, spores, biological or drug molecules, or chemical compounds). The label-free detection technology typically involves using a PWG sensor or a SPR sensor to detect a change in the refractive index of liquid or gas immediately above the sensor. For example, the change in refractive index can arise from a concentration change, surface adsorption, reaction, or the mere presence of a biological or chemical substance at the sensor's surface. Several types of known PWG sensors are described next each of which have different structures and materials of construction. And, then a description is provided about what causes a problematical signal drift which adversely affects the sensitivity of those PWG sensors. The cause of this problematical signal drift is addressed by the present invention.
In general, the PWG sensor is made from a substrate, a monomode waveguide and a sub-wavelength period diffraction grating that is formed into either the substrate or the waveguide. FIG. 1 (PRIOR ART) is a diagram which is used to help describe the basic elements and the basic functionality of one type of PWG sensor 100. As shown, the PWG sensor 100 has the following elements:                Substrate 102 (patterned with a sub-wavelength period diffraction grating 104).        Waveguide 106.        Chemically responsive surface chemistry layer 108.        Chemically bound molecules 110 (targets 110) of interest.        Solution 112 containing the substance 114 (analyte 114) to be detected.        
Typically, the thickness and refractive index of the waveguide 106 along with the characteristics (pitch, depth, and duty cycle) of the diffraction grating 104 are chosen to yield the highest possible sensitivity to a refractive index change which is caused by the interaction of the analyte 114 and target 110. This sensitivity is defined as the shift in the reflected light 116 relative to the refractive index change (nm/refractive index unit). Because, the sensing principle involves the interaction of an evanescent wave emerging from the waveguide 106, the sensed volume is typically limited to the first 150–200 nm above the surface of the waveguide 106. A more detailed discussion about the structure and the functionality of this PWG sensor 100 can be found in U.S. Pat. No. 4,815,843. The contents of this patent are incorporated by reference herein.
In the past, a lot of work has been done to enhance the performance of the PWG sensor 100. For example, it has been shown that the performance of the PWG sensor 100 can be enhanced by: (1) raising the index contrast between the substrate 102 and the waveguide 106 (see U.S. Patent Application 2005/0025421 and PCT Patent Application WO0235214); (2) producing a highly uniform diffraction grating 104 (see U.S. Pat. No. 6,873,764 B2); (3) lowering unfavorable interactions between the solution 112 containing the analyte 114 (molecules 114) of interest and the waveguide 106 which can result in resonant drift and other detrimental effects (see U.S. Pat. No. 6,332,363); and (4) increasing the amount of analyte 114 binding to the target 110 (receptor 110) by improving the surface chemistry layer 108 or its application (see U.S. Patent Application No. 2004/0043508A1).
In addition, a lot of work has been done in the past to make a disposable PWG sensor 100 so that one does not have to re-use the sensor 100 after performing an assay. This is desirable because if one re-uses the PWG sensor 100 then there is a possibility of cross-contamination. However, there are problems associated with manufacturing disposable PWG sensors 100 at a high yield and a low cost. And, there are problems associated with the performance of these disposable PWG sensors 100. These problems are described next.
The prior art demonstrates that there has been a struggle to balance the cost and performance in making a disposable PWG sensor 100. For instance, the PWG sensor 100 can have a low cost polymeric substrate 102 within which the sub-wavelength gratings 104 can be easily embossed or molded. However, the PWG sensor 100 which has a polymeric substrate 102 can suffer from a problematical optical signal loss that is due to absorption in the polymeric substrate 102. To address this absorption problem, the PWG sensor 100 can be enhanced by depositing a thick oxide or organic modified oxide layer between the polymeric substrate 102 and the waveguide 106. This type of PWG sensor 200 is illustrated in FIG. 2 (PRIOR ART). As shown, the PWG sensor 200 has the following elements:                Polymeric substrate 202 (patterned with a sub-wavelength period diffraction grating 204).        Inorganic cladding layer 205.        Waveguide 206.        Chemically responsive surface chemistry layer 208.        Chemically bound molecules 210 (targets 210) of interest.        Solution 212 containing the substance 214 (analyte 214) to be detected.        
For a more detailed discussion about the structure and the functionality of PWG sensor 200, reference is made to the following documents:                U.S. Pat. No. 5,369,722.        U.S. Pat. No. 6,804,445 B2.        
The contents of these documents are incorporated by reference herein.
Referring back to FIG. 1, it can be difficult to manufacture the PWG sensor 100 which has a polymeric substrate 102. In particular, there is a significant manufacturing challenge in keeping the polymeric substrate 102 flat to ensure a uniform coupling angle for the light 116 that is directed into and reflected out-off the PWG sensor 100. And, there is a significant manufacturing challenge in depositing the waveguide 106 onto the polymeric substrate 102 without damaging the polymeric substrate 102. To address these problems, the PWG sensor 100 can be enhanced by using a flat glass substrate 102 (which is more costly than a polymeric substrate 102) and then forming a polymeric layer onto the glass substrate 102 so the sub-wavelength diffraction grating 104 can be formed into the polymeric layer by embossing, UV curing, or molding. This type of PWG sensor 300 is illustrated in FIG. 3 (PRIOR ART). As shown, the PWG sensor 300 has the following elements:                Flat glass substrate 302.        Polymeric cladding layer 305 (patterned with a sub-wavelength period diffraction grating 304).        Waveguide 306.        Chemically responsive surface chemistry layer 308.        Chemically bound molecules 310 (targets 310) of interest.        Solution 312 containing the substance 314 (analyte 314) to be detected.        
The sensitivity of the PWG sensor 300 can be further enhanced if low index polymer layers (not shown) are used instead of the polymeric cladding layer 305. For a more detailed discussion about the structure and the functionality of these types of PWG sensors 300, reference is made to the following documents:                U.S. Patent Application No. 2003/0017580.        PCT Patent Application WO 0235214.        U.S. Patent Application No. 2005/0025421.        
The contents of these documents are incorporated by reference herein.
Referring again to FIG. 1, the PWG sensor 100 can be made where the diffraction grating 104 is directly formed into a flat glass substrate 102 by a photolithographic patterning and etching process. This type of PWG sensor 100 is costly but it is desirable because it uses a glass substrate 102 which does not have the flatness problem that is associated with a polymeric substrate 102. In addition, this type of PWG sensor 100 is more durable than the PWG sensor 100 which has the polymeric substrate 102. Because, the waveguide 106 can be deposited onto the glass substrate 102 without the strict restrictions on temperature and ion bombardment that are needed when the waveguide 106 is deposited onto a polymeric substrate 102.
However, the use of a photolithography patterning and etching process to form a smooth and accurately reproduced diffraction grating 104 on the top surface of the glass substrate 102 can be challenging. For example, a PWG sensor 100 has been made where ˜0.25 to 0.5 micron linewidths which are required for a subwavelength diffraction grating 104 have been formed in a glass substrate 102 by using a holographic photolithography process (see PCT Patent Application Nos. WO9809156 and WO02082130 and U.S. Pat. No. 6,873,764 B2). Unfortunately, this type of photolithography patterning process can be costly and as such it is not be suitable to manufacture disposable PWG sensors.
Moreover, the etching process which is used to form the diffraction grating 104 within the glass substrate 102 can be a significant challenge itself. For example, silicate glass substrates 102 can be etched by wet etching in a solution containing hydrofluoric acid, or by dry etching in a fluorine containing plasma. However, only simple glass substrates 102 like fused silica may be cleanly etched in this manner. In contrast, most commercial glass substrates 102 have compositions which are complex and contain alkali metals, alkaline earths, aluminum oxide, or transition metal oxides that do not etch well. In particular, the etching of these complex glasses by either a hydrofluoric acid containing solution or a fluorine containing plasma typically produces a rough etch surface, because the fluoride salts of the alkali metals, alkaline earths, aluminum and transition metals are not removed. However, clean features (such as diffraction gratings 104) can be etched for some compositions of glasses using mixed halide gases such as CCl2F2 when all of the etch products are volatile (see U.S. Pat. No. 6,873,764 B2). And, clean features (such as diffraction gratings 104) may also be plasma etched in some glasses under conditions where sputter etching is utilized (see J. Liu, N. I. Nemchuk, D. G. Ast, and J. G. Couillard, J. Non-Crystalline Solids 342 110 (2004)). Unfortunately, these plasma etching method are not practical for manufacturing large numbers of glass PWG sensors 100.
The aforementioned problems associated with etching clean diffraction gratings 104 in glass substrates 102 can be overcome by depositing a silica layer (which can be easily etched) or a polymer layer onto the glass substrate 102 and then patterning that layer by wet or dry etching. This type of PWG sensor 400 is illustrated in FIG. 4 (PRIOR ART). As shown, the PWG sensor 400 has the following elements:                Flat glass substrate 402.        Discontinuous oxide or polymer layer 405 (which also forms a sub-wavelength period diffraction grating 405).        Waveguide 406.        Chemically responsive surface chemistry layer 408.        Chemically bound molecules 410 (targets 410) of interest.        Solution 412 containing the substance 414 (analyte 414) to be detected.        
For a more detailed discussion about the structure and the functionality of PWG sensor 400, reference is made to the following document:                PCT Patent Application WO02082130.        
The contents of this document are incorporated by reference herein.
In many of the above PWG sensors, a surface layer (e.g., SiO2) may be deposited on top of the waveguide (e.g., PVD deposited Nb2O5) to facilitate the formation of a chemoresponsive layer. An exemplary PWG sensor 500 which has this surface layer is illustrated in FIG. 5 (PRIOR ART). As shown, the PWG sensor 500 has the following elements:                Flat glass substrate 502.        Polymer layer 505 (patterned with a sub-wavelength period diffraction grating 504).        Waveguide 506.        Surface layer 507.        Chemically responsive surface chemistry layer 508.        Chemically bound molecules 510 (targets 510) of interest.        Solution 512 containing the substance 514 (analyte 514) to be detected.        
For a more detailed discussion about the structure and the functionality of PWG sensor 500, reference is made to the following document:                U.S. Patent Application No. 2004/0043508A1.        
The contents of this document are incorporated by reference herein.
In all of the above PWG sensors, a key performance attribute is signal drift. Signal drift occurs when the high index waveguide (and if present the SiO2 surface layer) is porous or cracked which allows the interaction of the solution and the waveguide material. These pores and root cracks are always present in PVD deposited metal oxide waveguides which are deposited over gratings in polymer substrates (see FIG. 1), or deposited over polymer gratings which are on top of glass substrates (see FIG. 3). The pores result from the deposition of the waveguide at a low temperature and under a low ion flux. Under such conditions, adatoms from the vapor arrive at the growth surface and stay where they fall. This produces a columnar grain growth where the packing of adatoms is not optimal, resulting in porosity (see, D. L. Smith, Thin Film Deposition: Principles and Practice, McGraw-Hill (1995) 159–161).
A coating scientist can produce a fully dense oxide coating/waveguide by PVD if they can heat the substrate (typically 250° C. or above) to provide energy for surface diffusion of the adatoms to sites of higher binding energy, and/or if they can use ion bombardment to transfer momentum and pack the adatoms more densely (see D. L. Smith, Thin Film Deposition: Principles and Practice, McGraw-Hill, New York (1995) pp 119–180). However, these methods cannot be used in applications where polymer substrates and/or polymer gratings degrade at temperatures below 200° C. and under ion bombardment. This porosity problem is solved by the present invention.
Moreover, since this PVD coating process is a line of sight process, root cracks are often caused by inadequate step coverage over the grating features. These root cracks may cause signal drift due to infiltration of water during assays. A FIB image which is shown in FIG. 6 (PRIOR ART) illustrates two root cracks 602 that are in the waveguide layer 506 of the prior art PWG sensor 500. As can be seen, this PWG sensor 500 has a UV curable polymer grating 504 formed in a UV curable polymer 505 which is located on a glass substrate 502. FIG. 7 (PRIOR ART) has several plots which illustrate the signal drift (grating resonance vs. time) for 96 PWG sensors 500 (shown in FIGS. 5–6) that are located in a 96 well microplate which contains an aqueous solution. This root problem is solved by the present invention.
An engineering solution to cancel out the effects of signal drift caused by porosity and root cracks in PWG sensors 500 (for example) would be to reference the signal from within one half of each PWG sensor 500 to the other half, or from one PWG sensor 500 to other PWG sensors 500 that are incorporated in the wells of a microplate. For example, in the former solution part of each PWG sensor 500 may be covered or its surface chemistry altered to prevent binding of the target molecules. Then, these PWG sensors 500 would be interrogated. Alternatively, in the later solution a buffer solution can be added to all wells of a microplate, and the biological molecules only to some of the wells in the microplate. Then, the PWG sensors 500 in these wells would be interrogated. However, measurements of differential signal drift may only be used if each PWG sensor 500 in the microplate exhibits a similar signal drift when exposed to the same solutions. Unfortunately, as the plots in FIG. 8 (PRIOR ART) indicate, this is not the case for PWG sensors 500. These plots illustrate the intra-well referenced signal drift (grating resonance vs. time) for 96 PWG sensors 500 located in a 96 well microplate. Accordingly, there is a need to overcome the problematical signal drift that is associated with PWG sensors. This need and other needs are addressed by the present invention.